Histamine is widely distributed throughout the body and is involved in a variety of physiological and pathological conditions. In mammals, tissue mast cells are one of the major pools of histamine. While mast cells are found throughout the body, including the brain, our understanding of mast cell function and physiology is based almost exclusively on studies using peritoneal mast cells. This stems from the fact that peritoneal cells are easily obtained and readily purified. The function of mast cells in the brain is unknown. This research project will develop preparations which will enable histamine secretion from brain mast cells to be studied. Two approaches will be used. Isolation of mast cells from the brains of very young animals and their purification to homogeneity will be attempted using established tissue dissociation procedures and gradient centrifugation. Secondly, a system for perfusing brain tissue slices will be established. The effects of established mast cell secretagogues will be studied.